白血病细胞代谢异常成为研究热点，我们前期发现65%的初诊急性早幼粒细胞白血病(APL)病人存在血脂升高、随治疗加重，基因富集分析发现脂代谢通路异常，脂代谢关键基因PPARγ显著下调、参与APL致病的TRIB3基因显著上调，PML-RARA、TRIB3和PPARγ在核内共定位。文献报道RXR是PPARγ的靶基因。据此提出假说：PML-RARA和TRIB3协同抑制PPARγ-RXR轴的活化、促进脂代谢异常，维甲酸进一步抑制PPARγ的脂调控，而PPARγ激动剂在降脂的同时协同促进APL细胞凋亡。拟在APL细胞中证实PML-RARA和TRIB3协同抑制PPARγ-RXR轴的活化，而维甲酸处理后加重；在APL小鼠模型中证实存在脂代谢异常、PPARγ激动剂降脂的同时协同促进APL凋亡。对于揭示白血病脂代谢异常及治疗具有重要的基础和临床意义。

Recent studies have found that metabolic abnormalities are one of the characteristics of tumor cells and affect prognosis. It is of great significance to elucidate its molecular mechanisms and possible intervention targets. We found that 65% APL patients had abnormal dyslipidemia before treatment and was further aggravated after treatment. After analysis of differentially expressed genes, it was found that the lipid metabolism pathway was abnormally significant, and the key gene involved in lipid metabolism, PPARγ, was significantly down-regulated, while the TRIB3 gene involved in the pathology of APL was significantly up-regulated. We proposed hypothesis that the collaboration of PML-RARa and TRIB3 impedes the PPARg/RXR function and triggers dyslipidemia in acute promyelocytic leukemia. The aim of the study is as followings. 1. Confirmation of abnormal PPARγ signaling pathway in APL cell line and primary cells; 2. Transfection of PML-RARA into U937 cells, observation of changes inPPARγ and TRIB3 signaling pathways; 3. APL cells were treated with ATRA and Arsenic, and changes in PPARγ and TRIB3 signaling pathways were observed. 4. The presence of dyslipidemia was confirmed by PML-RARA transgenic mice, which are capable of lowering blood lipids and synergistically promoting apoptosis of APL. This study aims to clarify the molecular mechanism of lipid metabolism abnormalities in APL cells and possible therapeutic targets, which has important basic and clinical significance.